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[1]陽麗梅 黃旭慧 張倩文 陳淑芳.苦參堿預(yù)防大鼠膽汁淤積性肝損傷作用機(jī)制的研究[J].福建醫(yī)藥雜志,2019,41(05):8-12.
　YANG Limei,HUANG Xuhui,ZHANG Qianwen,et al.Matrine prevents cholestatic liver injury in rats[J].FUJIAN MEDICAL JOURNAL,2019,41(05):8-12.
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苦參堿預(yù)防大鼠膽汁淤積性肝損傷作用機(jī)制的研究()
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《福建醫(yī)藥雜志》[ISSN:1002-2600/CN:35-1071/R]

卷:
41
期數(shù):
2019年05期
頁碼:
8-12
欄目:
臨床研究
出版日期:
2019-10-15

文章信息/Info

Title:
Matrine prevents cholestatic liver injury in rats
文章編號:
1002-2600(2019)05-0008-05
作者:
陽麗梅 黃旭慧1; 2 張倩文3 陳淑芳1
福建醫(yī)科大學(xué)省立臨床醫(yī)學(xué)院 福建省立醫(yī)院藥學(xué)部(福州 350001)
Author(s):
YANG Limei;  HUANG Xuhui;  ZHANG Qianwen; CHEN Shufang
Department of Pharmacy,Fujian Provincial Hospital,Provincial Clinical Medical College of Fujian Medical University,Fuzhou, Fujian 350001,China
關(guān)鍵詞:
苦參堿;  膽汁淤積性肝損傷;  膽固醇7α-羥化酶;  法尼醇受體
Keywords:
matrine;  cholestasis;  cholesterol-7tr-hydroxylase;  farnesoid x receptor
分類號:
R332; R575
文獻(xiàn)標(biāo)志碼:
B
摘要:
目的 探討苦參堿(MT)預(yù)防膽汁淤積性肝損傷的作用機(jī)制。方法 將大鼠隨機(jī)分成生理鹽水(NS)組、ANIT模型組、熊去氧膽酸(UDCA)組、MT低劑量組(5 mg/kg)和MT高劑量組(10 mg/kg),采用α-萘異硫氫酸酯(ANIT)(60 mg/kg)建立膽汁淤積性肝損傷模型,連續(xù)灌胃給藥7天,實(shí)驗(yàn)結(jié)束前禁食24 h,不禁水,然后采血、取肝臟。全自動生化儀測定丙氨酸氨基轉(zhuǎn)移酶(ALT)、天冬氨酸氨基轉(zhuǎn)移酶(AST)、血清總膽紅素(TBiL)和堿性磷酸酶(ALP)水平,逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)(RT-PCR)法檢測大鼠肝臟中CYP7A1和FXR mRNA表達(dá),蛋白質(zhì)免疫印記(WB)法檢測大鼠肝臟中膽酸合成基因CYP7A1和FXR蛋白的表達(dá)。結(jié)果 與ANIT模型組相比,MT低、高劑量組ALT、AST、TBiL和ALP均明顯降低(P<0.01)。與ANIT模型組比較,UDCA組、MT低劑量組和MT高劑量組的FXR mRNA表達(dá)分別上調(diào)31%(P=0.059)、78%(P=0.001)、39%(P=0.05),CYP7A1 mRNA表達(dá)分別上調(diào)69%(P=0.102)、257%(P=0.005)和143%(P=0.024)。在蛋白表達(dá)水平,與ANIT模型組比較,UDCA組、MT低劑量組、MT高劑量組的FXR蛋白表達(dá)分別上調(diào)23%(P=0.065)、55%(P=0.005 6)和46%(P=0.035),而CYP7A1的蛋白表達(dá)分別下調(diào)34%(P=0.105)、42%(P=0.007 1)和5%(P=0.205)。結(jié)論 苦參堿預(yù)防大鼠膽汁淤積性肝損傷,可能通過調(diào)控FXR、CYPA7A1的基因及蛋白表達(dá)來實(shí)現(xiàn)。
Abstract:
Objective To determine the mechanism of matrine(MT)in preventing cholestatic liver injury.Methods α-naphthalene isothionate(ANIT)(60 mg/kg)was used to establish the cholestatic liver injury model in SD rats.All rats were randomly divided into four groups, which were normal saline(NS)group, ANIT model group, UDCA group, low-dose MT(5 mg/kg)group and high-dose MT(10 mg/kg)group.All rats were administered ANIT orally for seven days, fasting 24 h before the end, and their blood and livers were collected in the end.Automatic biochemical analyzer was used for detection of liver function indicators alanine aminotransferase(ALT), aspartate aminotransferase(AST),total bilirubin(TBiL)and alkaline phosphatase(ALP).RT-PCR was used to detect the mRNA expression of cholesterol synthesis 7α-hydroxylase(CYP7A1)and farnesoid receptor(FXR)in rat liver,and Western blot(WB)was used to detect the expression of CYP7A1 and FXR protein.Results Compared with ANIT model group,low-dose and high-dose MT decreased ALT, AST, TBiL and ALP significantly.FXR mRNA expression of UDCA, low-dose MT and high-dose MT groups increased by 31%(P=0.059), 78%(P=0.001)and 39%(P=0.05)than ANIT model group, while the CYP7A1 mRNA expression of these three groups increased by 69%(P=0.102), 257%(P=0.005)and 143%(P=0.024)than ANIT model group, respectively.FXR protein expression of UDCA, low-dose MT and high-dose MT groups increased by 23%(P=0.006 5), 55%(P=0.005 6)and 46%(P=0.035)than ANIT model group, while the CYP7A1 protein expression of these three groups decreased by 34%(P=0.105), 42%(P=0.007 1)and 5%(P=0.205)than ANIT model group, respectively.Conclusion MT could improve cholestatic liver injury in rats, the mechanism of which might be related to regulate the expression of FXR and CYP7A1 gene and protein.

參考文獻(xiàn)/References:

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備注/Memo

備注/Memo:
基金項目:福建省醫(yī)學(xué)創(chuàng)新課題(2016-CX-15) 1 福建省立金山醫(yī)院藥學(xué)部; 2 通信作者,Email:[email protected]; 3 福建醫(yī)科大學(xué)藥學(xué)院
更新日期/Last Update: 2019-10-15